The American Brachytherapy Society consensus statement for permanent implant brachytherapy using Yttrium-90 microsphere radioembolization for liver tumors



      To develop a multidisciplinary consensus for high quality multidisciplinary implementation of brachytherapy using Yttrium-90 (90Y) microspheres transarterial radioembolization (90Y TARE) for primary and metastatic cancers in the liver.


      Members of the American Brachytherapy Society (ABS) and colleagues with multidisciplinary expertise in liver tumor therapy formulated guidelines for 90Y TARE for unresectable primary liver malignancies and unresectable metastatic cancer to the liver. The consensus is provided on the most recent literature and clinical experience.


      The ABS strongly recommends the use of 90Y microsphere brachytherapy for the definitive/palliative treatment of unresectable liver cancer when recommended by the multidisciplinary team. A quality management program must be implemented at the start of 90Y TARE program development and follow-up data should be tracked for efficacy and toxicity. Patient-specific dosimetry optimized for treatment intent is recommended when conducting 90Y TARE. Implementation in patients on systemic therapy should account for factors that may enhance treatment related toxicity without delaying treatment inappropriately. Further management and salvage therapy options including retreatment with 90Y TARE should be carefully considered.


      ABS consensus for implementing a safe 90Y TARE program for liver cancer in the multidisciplinary setting is presented. It builds on previous guidelines to include recommendations for appropriate implementation based on current literature and practices in experienced centers. Practitioners and cooperative groups are encouraged to use this document as a guide to formulate their clinical practices and to adopt the most recent dose reporting policies that are critical for a unified outcome analysis of future effectiveness studies.


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        • Lee E.W.
        • Thakor A.S.
        • Tafti B.A.
        • Liu D.M.
        Y90 selective internal radiation therapy.
        Surg Oncol Clin N Am. 2015; 24: 167-185
        • Liu D.M.
        • Salem R.
        • Bui J.T.
        • et al.
        Angiographic considerations in patients undergoing liver-directed therapy.
        J Vasc Interv Radiol. Jul 2005; 16: 911-935
        • Lewandowski R.J.
        • Sato K.T.
        • Atassi B.
        • et al.
        Radioembolization with 90Y microspheres: angiographic and technical considerations.
        Cardiovasc Intervent Radiol. Jul-Aug 2007; 30: 571-592
        • Berger M.J.
        • Coursey J.S.
        • Zucker M.A.
        • Chang J.
        ESTAR, PSTAR, and ASTAR: computer programs for calculating stopping-power and range tables for electrons, protons, and helium ions.
        • Erbe E.M.
        • Day D.E.
        Chemical durability of Y2O3-Al2O3-SiO2 glasses for the in vivo delivery of beta radiation.
        J Biomed Mater Res. Oct 1993; 27: 1301-1308
      1. Biocompatibles; Therasphere (TM). Package Insert. Biocompatibles UK Ltd, Chapman House Farnham Business Park Weydon Lane FARNHAM, GU9 8QL United Kingdom, 2014.

      2. Day D.E., Ehrhardt G.J. Microspheres for radiation therapy. 1994.

        • Sirtex
        SIR-Sphere (TM). package insert.
        Sirtex Medical Inc. 2011;
      3. Gray B.N. Method of treating cancer. 2014.

      4. SIR-Sphere (TM). package insert.
        Sirtex Medical Inc. 2011;
        • Ahmadzadehfar H.
        • Meyer C.
        • Pieper C.C.
        • et al.
        Evaluation of the delivered activity of yttrium-90 resin microspheres using sterile water and 5% glucose during administration.
        EJNMMI Res. 2015; 5 (2015/10/13): 54
        • Koran M.E.
        • Stewart S.
        • Baker J.C.
        • et al.
        Five percent dextrose maximizes dose delivery of Yttrium-90 resin microspheres and reduces rates of premature stasis compared to sterile water.
        Biomed Rep. 2016; 5 (2016/12): 745-748
        • Paprottka K.J.
        • Lehner S.
        • Fendler W.P.
        • et al.
        Reduced periprocedural analgesia after replacement of water for injection with glucose 5% solution as the infusion medium for 90Y-resin microspheres.
        J Nucl Med. 2016; 57 (2016/11/01): 1679-1684
        • Helling T.S.
        • Martin M.
        Cause of death from liver metastases in colorectal cancer.
        Ann Surg Oncol. 2014; 21: 501-506
        • Abdalla E.K.
        • Vauthey J.N.
        • Ellis L.M.
        • et al.
        Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases.
        Ann Surg. 2004; 239 (discussion 25-7): 818-825
        • Ruers T.
        • Van Coevorden F.
        • Punt C.J.
        • et al.
        Local Treatment of unresectable colorectal liver metastases: results of a randomized phase II trial.
        J Natl Cancer Inst. 2017; 109: 1-10
        • Gibbs P.
        • Do C.
        • Lipton L.
        • et al.
        Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma.
        BMC Cancer. 2015; 15: 802
        • Tempero M.A.
        • Arnoletti J.P.
        • Behrman S.W.
        • et al.
        Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN guidelines.
        J Natl Compr Canc Netw. 2012; 10: 703-713
        • Seufferlein T.
        • Porzner M.
        • Becker T.
        • et al.
        [S3-guideline exocrine pancreatic cancer].
        Z Gastroenterol. 2013; 51: 1395-1440
        • Sangha B.S.
        • Nimeiri H.
        • Hickey R.
        • et al.
        Radioembolization as a treatment strategy for metastatic colorectal cancer to the liver: what can we learn from the SIRFLOX trial?.
        Curr Treat Options Oncol. 2016; 17 (06): 26
        • van Hazel G.A.
        • Heinemann V.
        • Sharma N.K.
        • et al.
        SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 (Plus or Minus Bevacizumab) versus mFOLFOX6 (Plus or Minus Bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer.
        J Clin Oncol. 2016; 34 (05): 1723-1731
        • Kennedy A.
        • Cohn M.
        • Coldwell D.M.
        • et al.
        Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.
        J Gastrointest Oncol. 2017; 8: 614-624
        • Salem R.
        • Gabr A.
        • Riaz A.
        • et al.
        Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience.
        Hepatology. 2018; 68: 1429-1440
        • Teyateeti A.
        • Mahvash A.
        • Long J.P.
        • et al.
        Survival outcomes for Yttrium-90 transarterial radioembolization with and without sorafenib for unresectable hepatocellular carcinoma patients.
        J Hepatocell Carcinoma. 2020; 7: 117-131
        • Wasan H.S.
        • Gibbs P.
        • Sharma N.K.
        • et al.
        First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials.
        Lancet Oncol. 2017; 18 (09): 1159-1171
        • Cucchetti A.
        • Sposito C.
        • Pinna A.D.
        • et al.
        Competing risk analysis on outcome after hepatic resection of hepatocellular carcinoma in cirrhotic patients.
        World J Gastroenterol. 2017; 23: 1469-1476
        • Malhotra A.
        • Liu D.M.
        • Talenfeld A.D.
        Radiation segmentectomy and radiation lobectomy: a practical review of techniques.
        Tech Vasc Interv Radiol. 2019; 22: 49-57
        • Padia S.A.
        • Lewandowski R.J.
        • Johnson G.E.
        • et al.
        Radioembolization of hepatic malignancies: background, quality improvement guidelines, and future directions.
        J Vasc Interv Radiol. 2017; 28: 1-15
        • Bishay V.L.
        • Biederman D.M.
        • Ward T.J.
        • et al.
        Transradial approach for hepatic radioembolization: initial results and technique.
        AJR Am J Roentgenol. 2016; 207: 1112-1121
        • Ng E.
        • Chung J.
        • Klass D.
        • et al.
        Optimized computed tomographic angiography vessel evaluation protocol (OCTAVE) prior to trans­arterial radioembolization.
        Intervent Oncol. 2016; 360 (4): E183-EE93
        • Hamoui N.
        • Minocha J.
        • Memon K.
        • et al.
        Prophylactic embolization of the gastroduodenal and right gastric arteries is not routinely necessary before radioembolization with glass microspheres.
        J Vasc Interv Radiol. 2013; 24: 1743-1745
        • Schelhorn J.
        • Theysohn J.
        • Ertle J.
        • et al.
        Selective internal radiation therapy of hepatic tumours: is coiling of the gastroduodenal artery always beneficial?.
        Clin Radiol. 2014; 69: e216-e222
        • Borggreve A.S.
        • Landman A.
        • Vissers C.M.J.
        • et al.
        Radioembolization: is prophylactic embolization of hepaticoenteric arteries necessary? A systematic review.
        Cardiovasc Intervent Radiol. 2016; 39: 696-704
        • Fischman A.
        • Patel R.
        • Kim E.
        COSY trial: a prospective, randomized study of coilng vs surefire infusion system in Y90.
        J Vasc and Interventional Radiol. 2014; 25: S107-SS08
        • Bhalani S.M.
        • Lewandowski R.J.
        Radioembolization complicated by nontarget embolization to the falciform artery.
        Semin Intervent Radiol. 2011; 28: 234-239
        • Wang D.S.
        • Louie J.D.
        • Kothary N.
        • et al.
        Prophylactic topically applied ice to prevent cutaneous complications of nontarget chemoembolization and radioembolization.
        J Vasc Interv Radiol. 2013; 24: 596-600
        • Louie J.D.
        • Kothary N.
        • Kuo W.T.
        • et al.
        Incorporating cone-beam CT into the treatment planning for yttrium-90 radioembolization.
        J Vasc Interv Radiol. 2009; 20: 606-613
        • Ahmadzadehfar H.
        • Sabet A.
        • Biermann K.
        • et al.
        The significance of 99mTc-MAA SPECT/CT liver perfusion imaging in treatment planning for 90Y-microsphere selective internal radiation treatment.
        J Nucl Med. 2010; 51: 1206-1212
        • Haggerty J.E.
        • Vaidya S.
        • Kooy T.
        • et al.
        Identification of the falciform artery on nuclear medicine imaging with successful coil embolization for planned Y-90 therapy.
        Clin Nucl Med. 2012; 37: 105-107
        • Haste P.
        • Tann M.
        • Persohn S.
        • et al.
        Correlation of Technetium-99m macroaggregated albumin and Yttrium-90 glass microsphere biodistribution in hepatocellular carcinoma: a retrospective review of pretreatment single photon emission CT and posttreatment positron emission tomography/CT.
        J Vasc Interv Radiol. 2017; 28 (e1): 722-730
        • Yu N.
        • Srinivas S.M.
        • DiFilippo F.P.
        • et al.
        Lung dose calculation with SPECT/CT for 90Yittrium radioembolization of liver cancer.
        Int J Radiation Oncol*Biol*Physics. 2013; 85 (2013/03/01): 834-839
        • Elschot M.
        • Nijsen J.F.W.
        • Lam M.G.E.H.
        • et al.
        99mTc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with 166Ho-microspheres.
        Eur J Nucl Med Mol Imaging. 2014; 41 (2014/05/13): 1965-1975
        • Kao Y.H.
        • Magsombol B.M.
        • Toh Y.
        • et al.
        Personalized predictive lung dosimetry by technetium-99m macroaggregated albumin SPECT/CT for yttrium-90 radioembolization.
        EJNMMI Res. 2014; 4 (2014/06/29): 33
        • Allred J.D.
        • Niedbala J.
        • Mikell J.K.
        • et al.
        The value of 99mTc-MAA SPECT/CT for lung shunt estimation in 90Y radioembolization: a phantom and patient study.
        EJNMMI Res. 2018; 8 (2018/06/15): 50
        • Dittmann H.
        • Kopp D.
        • Kupferschlaeger J.
        • et al.
        A prospective study of quantitative SPECT/CT for evaluation of lung shunt fraction before SIRT of liver tumors.
        J Nucl Med. 2018; 59 (2018/09/01): 1366-1372
        • Lopez B.
        • Mahvash A.
        • Lam M.
        • Kappadath S.C.
        Calculation of lung mean dose and quantification of error for (90) Y-microsphere radioembolization using (99m) Tc-MAA SPECT/CT and diagnostic chest CT.
        Med Phys. 2019; 46: 3929-3940
        • Ho C.L.
        • Chen S.
        • Cheung S.K.
        • et al.
        Radioembolization with 90Y glass microspheres for hepatocellular carcinoma: significance of pretreatment 11C-acetate and 18F-FDG PET/CT and posttreatment 90Y PET/CT in individualized dose prescription.
        Eur J Nucl Med Mol Imaging. 2018; 45 (2018/11/01): 2110-2121
        • Busse N.
        • Erwin W.
        • Pan T
        Evaluation of a semiautomated lung mass calculation technique for internal dosimetry applications.
        Med Phys. 2013; 40 (2013/12/01)122503
        • Bastiaannet R.
        • Viergever M.A.
        • dHWAM Jong
        Impact of respiratory motion and acquisition settings on SPECT liver dosimetry for radioembolization.
        Med Phys. 2017; 44 (2017/10/01): 5270-5279
        • Mikell J.K.
        • Mahvash A.
        • Siman W.
        Comparing voxel-based absorbed dosimetry methods in tumors, liver, lung, and at the liver-lung interface for (90)Y microsphere selective internal radiation therapy.
        EJNMMI Phys. Dec 2015; 2: 16
        • Kappadath S.C.
        • Lopez B.P.
        • Salem R.
        • Lam M.G.
        Lung shunt and lung dose calculation methods for radioembolization treatment planning.
        Q J Nucl Med Mol Imaging. 2021; 65: 32-42
        • Kappadath S.C.
        • Lopez B.P.
        • Salem R.
        • Lam M.G.E.H.
        Reassessment of the lung dose limits for radioembolization.
        Nucl Med Commun. 2021; 42: 1064-1075
        • Lam M.G.
        • Banerjee A.
        • Goris M.L.
        • et al.
        Fusion dual-tracer SPECT-based hepatic dosimetry predicts outcome after radioembolization for a wide range of tumour cell types.
        Eur J Nucl Med Mol Imaging. Jul 2015; 42: 1192-1201
        • Willowson K.P.
        • Schembri G.P.
        • Bernard E.J.
        • Chan D.L.
        Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [(99m)Tc]TcMebrofenin.
        Eur J Nucl Med Mol Imaging. Apr 2020; 47: 838-848
        • Gulec S.A.
        • Sztejnberg M.L.
        • Siegel J.A.
        Hepatic structural dosimetry in (90)Y microsphere treatment: a Monte Carlo modeling approach based on lobular microanatomy.
        J Nucl Med. 2010; 51: 301-310
        • Liu D.
        • Klass D.
        • Westcott M.
        • Kennedy A.S.
        The limitations of theoretical dose modeling for yttrium-90 radioembolization.
        J Vasc Interv Radiol. 2014; 25: 1146-1147
        • Henry E.
        • Strugari M.
        • Mawko G.
        • et al.
        Post-administration dosimetry in yttrium-90 radioembolization through micro-CT imaging of radiopaque microspheres in a porcine renal model.
        Phys Med Biol. 2021; 66
        • Westcott M.A.
        • Coldwell D.M.
        • Liu D.M.
        • Zikria J.F.
        The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres.
        Adv Radiat Oncol. 2016; 1: 351-364
        • Liu D.
        • Westcott M.
        • Garcia-Monaco R.
        • Abraham R.
        Down and dirty with Dosimetry A practical understanding and approach to radioembolization.
        Endovascular Today. 2016; : 15
        • Lam M.G.E.H.
        • Louie J.D.
        • Abdelmaksoud M.H.K.
        Limitations of body surface area–based activity calculation for radioembolization of hepatic metastases in colorectal cancer.
        J Vasc and Interventional Radiol. 2014; 25 (2014/07): 1085-1093
        • Ho S.
        • Lau W.Y.
        • Leung T.W.
        • et al.
        Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours.
        Eur J Nucl Med. 1996; 23 (1996/08): 947-952
        • Bolch W.E.
        • Bouchet L.G.
        • Robertson J.S.
        MIRD Pamphlet No. 17: the dosimetry of nonuniform activity distributions–radionuclide s values at the voxel level.
        J Nucl Med. 1999; 40 (1999/01/01): 11S-136
        • Dieudonne A.
        • Hobbs R.F.
        • Bolch W.E.
        Fine-resolution voxel s values for constructing absorbed dose distributions at variable voxel size.
        J Nucl Med. 2010; 51 (2010/10/01): 1600-1607
      5. Amato E., Minutoli F., Pacilio M., et al. An analytical method for computing voxel S values for electrons and photons. Med Physics. 2012 2012/11/01;39:6808–17.

        • Lanconelli N.
        • Pacilio M.
        • Lo Meo S.
        A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions.
        Phys Med Biol. 2012; 57 (2012/01/21): 517-533
        • Sanchez-Garcia M.
        • Gardin I.
        • Lebtahi R.
        • Dieudonné A.
        A new approach for dose calculation in targeted radionuclide therapy (TRT) based on collapsed cone superposition: validation with 90Y.
        Phys Med Biol. 2014; 59 (2014/09/07): 4769
        • Mikell J.
        • Kappadath S.C.
        • Wareing T.
        Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine.
        Phys Med Biol. 2016; 61 (2016): 4564
        • Prideaux A.R.
        • Song H.
        • Hobbs R.F.
        Three-dimensional radiobiologic dosimetry: application of radiobiologic modeling to patient-specific 3-dimensional imaging-based internal Dosimetry.
        J Nucl Med. 2007; 48 (2007/06/01): 1008-1016
        • Pasciak A.S.
        • Erwin W.D.
        Effect of voxel size and computation method on Tc-99m MAA SPECT/CT-based dose estimation for Y-90 microsphere therapy.
        IEEE Trans Med Imaging. 2009; 28 (2009/11): 1754-1758
        • Dieudonné A.
        • Hobbs R.F.
        • Lebtahi R.
        Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct Monte Carlo methods.
        J Nucl Med. 2013; 54 (2013/02/01): 236-243
        • Mikell J.K.
        • Mahvash A.
        • Siman W.
        Selective internal radiation therapy with yttrium-90 glass microspheres: biases and uncertainties in absorbed dose calculations between clinical dosimetry models.
        Int J Radiation Oncol*Biol*Physics. 2016; 96 (2016/11/15): 888-896
        • Allimant C.
        • Kafrouni M.
        • Delicque J.
        • et al.
        Tumor targeting and three-dimensional voxel-based dosimetry to predict tumor response, toxicity, and survival after Yttrium-90 resin microsphere radioembolization in hepatocellular carcinoma.
        J Vasc and Interventional Radiol. 2018; 29 (2018/12/01e4.): 1662-1670
        • Siman W.
        • Mawlawi O.R.
        • Mikell J.K.
        • Mourtada F.
        Effects of image noise, respiratory motion, and motion compensation on 3D activity quantification in count-limited PET images.
        Phys Med Biol. 2017; 62 (2017): 448
        • Siman W.
        • Mawlawi O.R.
        • Mourtada F.
        • Kappadath S.C.
        Systematic and random errors of PET-based (90) Y 3D dose quantification.
        Med Phys. 2020; 47: 2441-2449
        • Kappadath S.C.
        • Mikell J.
        • Balagopal A.
        Hepatocellular carcinoma tumor dose response after (90)Y-radioembolization with glass microspheres using (90)Y-SPECT/CT-based voxel dosimetry.
        Int J Radiat Oncol Biol Phys. 2018; 102: 451-461
        • Balagopal A.
        • Kappadath S.C.
        Characterization of 90Y-SPECT/CT self-calibration approaches on the quantification of voxel-level absorbed doses following 90Y-microsphere selective internal radiation therapy.
        Med Phys. 2017; 45: 875-883
        • Lhommel R.
        • vL Elmbt
        • Goffette P.
        Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-Spheres.
        Eur J Nucl Med Mol Imaging. 2010; 37 (2010/08/01): 1654-1662
        • Fourkal E.
        • Veltchev I.
        • Lin M.
        3D inpatient dose reconstruction from the PET-CT imaging of 90Y microspheres for metastatic cancer to the liver: feasibility study.
        Med Phys. 2013; 40081702
      6. Carlier T., Willowson K.P., Fourkal E., et al. 90Y -PET imaging: exploring limitations and accuracy under conditions of low counts and high random fraction. Medical Physics. 2015 2015/07/01;42:4295–309.

        • Willowson K.P.
        • Tapner M.
        • Bailey D.L.
        A multicentre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization with resin microspheres.
        Eur J Nucl Med Mol Imaging. 2015; 42 (2015): 1202-1222
        • D'Arienzo M.
        • Chiaramida P.
        • Chiacchiararelli L.
        90Y PET-based dosimetry after selective internal radiotherapy treatments.
        Nuclear Medicine Communications June 2012. 2012; 33 (2012): 633-640
        • Siman W.
        • Kappadath S.C.
        Comparison of step-and-shoot and continuous-bed-motion PET modes of acquisition for limited-view organ scans.
        J Nucl Med Technol. Dec 2017; 45: 290-296
        • Siman W.
        • Mikell J.K.
        • Mawlawi O.R.
        Dose volume histogram-based optimization of image reconstruction parameters for quantitative (90) Y-PET imaging.
        Med Phys. 2019; 46: 229-237
        • Siman W.
        • Mikell J.K.
        • Kappadath S.C.
        Practical reconstruction protocol for quantitative 90Y bremsstrahlung SPECT/CT.
        Med. Phys. 2016; : 5093-5103
      7. 2016/09/01.
        • Rong X.
        • Du Y.
        • Ljungberg M.
        Development and evaluation of an improved quantitative [sup 90]Y bremsstrahlung SPECT method.
        Med Phys. 2012; 39 (2012): 2346-2358
        • Elschot M.
        • Lam M.G.E.H.
        • vdMAAJ Bosch
        Quantitative Monte Carlo–based 90Y SPECT reconstruction.
        J Nucl Med. 2013; : 1557-1563
      8. 2013/09/01.
        • Dewaraja Y.K.
        • Chun S.Y.
        • Srinivasa R.N.
        Improved quantitative 90Y bremsstrahlung SPECT/CT reconstruction with Monte Carlo scatter modeling.
        Med Phys. 2017; 12 (2017/44): 6364-6376
        • Lim H.
        • Fessler J.A.
        • Wilderman S.J.
        Y-90 SPECT ML image reconstruction with a new model for tissue-dependent bremsstrahlung production using CT information: a proof-of-concept study.
        Phys Med Biol. 2018; 63 (2018)115001
        • Ng S.C.
        • Lee V.H.
        • Law M.W.
        Patient dosimetry for 90Y selective internal radiation treatment based on 90Y PET imaging.
        J Appl Clin Med Phys. 2013; 14: 212-221
        • Martí-Climent J.M.
        • Prieto E.
        • Elosúa C.
        PET optimization for improved assessment and accurate quantification of 90Y-microsphere biodistribution after radioembolization.
        Med Phys. 2014; 41092503
        • Wright C.L.
        • Zhang J.
        • Binzel K.
        90Y Digital PET/CT imaging following radioembolization.
        Clin Nucl Med. 2016; 41: 975-976
        • Knešaurek K.
        • Tuli A.
        • Kim E.
        • et al.
        Comparison of PET/CT and PET/MR imaging and dosimetry of yttrium-90 (90Y) in patients with unresectable hepatic tumors who have received intra-arterial radioembolization therapy with 90Y microspheres.
        EJNMMI Phys. 2018; 5: 23
        • Eckerman K.
        • Endo A.
        ICRP Publication 107. Nuclear decay data for dosimetric calculations.
        Ann ICRP. 2008 2008; 38: 7-96
        • Zanzonico P.B.
        • Binkert B.L.
        • Goldsmith S.J.
        Bremsstrahlung radiation exposure from pure β-Ray emitters.
        J Nucl Med. 1999; 40 (1999/06/01): 1024-1028
        • Gulec S.A.
        • Siegel J.A.
        Posttherapy radiation safety considerations in radiomicrosphere treatment with 90Y-microspheres.
        J Nucl Med. 2007; 48 (2007/12/01): 2080-2086
        • Dezarn W.A.
        • Cessna J.T.
        • DeWerd L.A.
        Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for [sup 90]Y microsphere brachytherapy in the treatment of hepatic malignancies.
        Med Phys. 2011; 38 (2011): 4824-4845
        • Giammarile F.
        • Bodei L.
        • Chiesa C.
        EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.
        Eur J Nucl Med Mol Imaging. 2011; 38 (2011/04/15): 1393-1406
      9. Erwin W.D. Radiation safety concerns associated with preparing the dosage, treating and releasing the patient, and managing radioactive waste. Handbook of Radioembolization 2016.

        • Thomas M.A.
        • Mahvash A.
        • Abdelsalam M.
        Planning dosimetry for (90) Y radioembolization with glass microspheres: evaluating the fidelity of (99m) Tc-MAA and partition model predictions.
        Med Phys. 2020; 47: 5333-5342
        • Mahvash A.
        • Chartier S.
        • Turco M.
        A prospective, multicenter, open-label, clinical trial design to evaluate the safety and efficacy of 90Y resin microspheres for treatment of unresectable hepatocellular carcinoma (HCC): dOORwaY90.
        HPB. 2021; 23: S545-SS46
        • Salem R.
        • Padia S.A.
        • Lam M.
        Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group.
        Eur J Nucl Med Mol Imaging. 2019; 46: 1695-1704
        • Levillain H.
        • Bagni O.
        • Deroose C.M.
        International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.
        Eur J Nucl Med Mol Imaging. 2021; 48: 1570-1584
        • Lam M.G.
        • Abdelmaksoud M.H.
        • Chang D.T.
        Safety of 90Y radioembolization in patients who have undergone previous external beam radiation therapy.
        Int J Radiat Oncol Biol Phys. 2013; 87: 323-329
        • Wang T.H.
        • Huang P.I.
        • Hu Y.W.
        Combined Yttrium-90 microsphere selective internal radiation therapy and external beam radiotherapy in patients with hepatocellular carcinoma: from clinical aspects to dosimetry.
        PLoS ONE. 2018; 13e0190098
        • Dritschilo A.
        • Grant E.G.
        • Harter K.W.
        Interstitial radiation therapy for hepatic metastases: sonographic guidance for applicator placement.
        AJR Am J Roentgenol. 1986; 147: 275-278
        • Ricke J.
        • Wust P.
        • Stohlmann A.
        CT-guided interstitial brachytherapy of liver malignancies alone or in combination with thermal ablation: phase I-II results of a novel technique.
        Int J Radiat Oncol Biol Phys. 2004; 58: 1496-1505
        • Ricke J.
        • Wust P.
        • Wieners G.
        Liver malignancies: cT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation.
        J Vasc Interv Radiol. 2004; 15: 1279-1286
        • Mohnike K.
        • Wieners G.
        • Schwartz F.
        Computed tomography-guided high-dose-rate brachytherapy in hepatocellular carcinoma: safety, efficacy, and effect on survival.
        Int J Radiat Oncol Biol Phys. 2010; 78: 172-179
        • Ricke J.
        • Mohnike K.
        • Pech M.
        Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy.
        Int J Radiat Oncol Biol Phys. 2010; 78: 479-485
        • Collettini F.
        • Singh A.
        • Schnapauff D.
        Computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of metastases adjacent to the liver hilum.
        Eur J Radiol. 2013; 82: e509-e514
        • Tselis N.
        • Chatzikonstantinou G.
        • Kolotas C.
        Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study.
        Eur Radiol. 2013; 23: 2264-2270
        • Tselis N.
        • Chatzikonstantinou G.
        • Kolotas C.
        Hypofractionated accelerated computed tomography-guided interstitial high-dose-rate brachytherapy for liver malignancies.
        Brachytherapy. 2012; 11: 507-514
        • Powerski M.
        • Penzlin S.
        • Hass P.
        Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors: a systematic analysis of 102 cases.
        Strahlenther Onkol. 2019; 195: 265-273
        • Damm R.
        • El-Sanosy S.
        • Omari J.
        Ultrasound-assisted catheter placement in CT-guided HDR brachytherapy for the local ablation of abdominal malignancies: initial experience.
        Rofo. 2019; 191: 48-53
        • Collettini F.
        • Jonczyk M.
        • Meddeb A.
        Feasibility and safety of CT-guided high-dose-rate brachytherapy combined with transarterial chemoembolization using irinotecan-loaded microspheres for the treatment of large, unresectable colorectal liver metastases.
        J Vasc Interv Radiol. Feb 2020; 31: 315-322
        • Rhim H.
        • Goldberg S.N.
        • Dodd 3rd, G.D.
        Essential techniques for successful radio-frequency thermal ablation of malignant hepatic tumors.
        Radiographics. 2001; (Oct21 Spec Nodiscussion S36-9): S17-S35
        • Kuvshinoff B.W.
        • Ota D.M.
        Radiofrequency ablation of liver tumors: influence of technique and tumor size.
        Surgery. 2002; 132 (discussion 11-2): 605-611
        • Pan C.C.
        • Kavanagh B.D.
        • Dawson L.A.
        Radiation-associated liver injury.
        Int J Radiat Oncol Biol Phys. 2010 Mar 1; 76 (Suppl): S94-100
        • Kennedy A.
        Radioembolization of hepatic tumors.
        J Gastrointest Oncol. 2014; 5: 178-189
        • Kennedy A.S.
        Radiation oncology approaches in liver malignancies.
        Am Soc Clin Oncol Educ Book. 2014; : e150-e155
        • Collettini F.
        • Schnapauff D.
        • Poellinger A.
        Hepatocellular carcinoma: computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of large (5-7cm) and very large (>7cm) tumours.
        Eur Radiol. 2012; 22: 1101-1109
        • Pardo F.
        • Sangro B.
        • Lee R.C.
        • et al.
        The Post-SIR-Spheres Surgery Study (P4S): retrospective analysis of safety following hepatic resection or transplantation in patients previously treated with selective internal radiation therapy with yttrium-90 resin microspheres.
        Annals of surgical oncology. 2017; 24 (9): 2465-2473
        • Kishi Yoji
        • Vauthey Jean-Nicolas
        Issues to be considered to address the future liver remnant prior to major hepatectomy.
        Surgery Today. 2021; 51 (4): 472-484
        • Madoff D.C.
        • David C.
        • Abdalla Ek Fau
        • Vauthey Jean-Nicolas
        Portal vein embolization in preparation for major hepatic resection: evolution of a new standard of care.
        Journal of vascular and interventional radiology. 2005; 16 (6): 779-790
        • Gabr A.
        • Polineni P.
        • Mouli S.K.
        • et al.
        Neoadjuvant radiation lobectomy as an alternative to portal vein embolization in hepatocellular carcinoma.
        Seminars in nuclear medicine. 2019; 49
        • Zhang E.
        • Wang L.
        • Shaikh T.
        • et al.
        Neoadjuvant chemoradiation impacts the prognostic effect of surgical margin status in pancreatic adenocarcinoma.
        Annals of surgical oncology. 2022; 29 (1): 354-363
        • Gibbs P.
        • Heinemann V.
        • Sharma N.K.
        Effect of primary tumor side on survival outcomes in untreated patients with metastatic colorectal cancer when selective internal radiation therapy is added to chemotherapy: combined analysis of two randomized controlled studies.
        Clin Colorectal Cancer. 2018; 12: e617-ee29
        • Sofocleous C.T.
        • Garcia A.R.
        • Pandit-Taskar N.
        • et al.
        Phase I trial of selective internal radiation therapy for chemorefractory colorectal cancer liver metastases progressing after hepatic arterial pump and systemic chemotherapy.
        Clinical Colorectal Cancer. 2014; 13 (1): 27-36
        • Dhir M.
        • Zenati M.S.
        • Jones H.L.
        • et al.
        Effectiveness of hepatic artery infusion (HAI) versus selective internal radiation therapy (Y90) for pretreated isolated unresectable colorectal liver metastases (IU-CRCLM).
        Annals of Surgical Oncology. 2018; 25 (2): 550-557
        • Kulik L.M.
        • Atassi B.
        • van Holsbeeck L.
        Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation.
        J Surg Oncol. 2006; 94: 572-586
        • Ricke J.
        • Klumpen H.J.
        • Amthauer H.
        Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma.
        J Hepatol. 2019; 71: 1164-1174
        • Henry L.R.
        • Hostetter R.B.
        • Ressler B.
        Liver resection for metastatic disease after y90 radioembolization: a case series with long-term follow-up.
        Ann Surg Oncol. 2015; 22: 467-474
        • Garlipp B.
        • Gibbs P.
        • Van Hazel G.A.
        Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.
        Br J Surg. 2019; 12: 1837-1846
        • Engelsman M.
        • Schwarz M.
        • Dong L.
        Physics controversies in proton therapy.
        Semin Radiat Oncol. 2013; 23: 88-96
        • Dawson L.A.
        • Normolle D.
        • Balter J.M.
        Ten Haken RK. Analysis of radiation-induced liver disease using the Lyman NTCP model.
        Int J Radiat Oncol Biol Phys. 2002; 53: 810-821
        • Dawson L.A.
        • Ten Haken RK
        Partial volume tolerance of the liver to radiation.
        Semin Radiat Oncol. 2005; 15: 279-283
        • Mizumoto M.
        • Okumura T.
        • Hashimoto T.
        Evaluation of liver function after proton beam therapy for hepatocellular carcinoma.
        Int J Radiat Oncol Biol Phys. 2012 Mar 1; 82: e529-e535
        • Mizumoto M.
        • Okumura T.
        • Hashimoto T.
        Proton beam therapy for hepatocellular carcinoma: a comparison of three treatment protocols.
        Int J Radiat Oncol Biol Phys. 2011; 81: 1039-1045
        • Makita C.
        • Nakamura T.
        • Takada A.
        Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma.
        Radiat Oncol. 2014; 9: 26
        • Apisarnthanarax S.
        • Bowen S.R.
        • Combs S.E.
        Proton beam therapy and carbon ion radiotherapy for hepatocellular carcinoma.
        Semin Radiat Oncol. 2018; 28: 309-320
        • Chadha A.S.
        • Gunther J.R.
        • Hsieh C.E.
        Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma.
        Radiother Oncol. 2019; 133: 54-61
        • Chuong M.D.
        • Kaiser A.
        • Khan F.
        Consensus report from the Miami liver proton therapy conference.
        Front Oncol. 2019; 9: 457
        • Sanford N.N.
        • Pursley J.
        • Noe B.
        Protons versus photons for unresectable hepatocellular carcinoma: liver decompensation and overall survival.
        Int J Radiat Oncol Biol Phys. 2019; 105: 64-72
        • Komatsu S.
        • Fukumoto T.
        • Demizu Y.
        Clinical results and risk factors of proton and carbon ion therapy for hepatocellular carcinoma.
        Cancer. 2011; 117: 4890-4904
      10. ASTRO. Model policy for proton beam therapy. 2018.

        • Hong T.S.
        • Wo J.Y.
        • Borger D.R.
        Phase II study of proton-based stereotactic body radiation therapy for liver metastases: importance of tumor genotype.
        JNCI: Journal of the National Cancer Institute. 2017; 109 (9djx031)
        • Kawashima M.
        • Furuse J.
        • Nishio T.
        Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma.
        J Clin Oncol. 2005; 23: 1839-1846
        • Hong T.S.
        • Wo J.Y.
        • Yeap B.Y.
        Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
        J Clin Oncol. 2016; 34: 460-468
        • Sugahara S.
        • Oshiro Y.
        • Nakayama H.
        Proton beam therapy for large hepatocellular carcinoma.
        Int J Radiat Oncol Biol Phys. 2010; 76: 460-466
        • Nakamura M.
        • Fukumitsu N.
        • Kamizawa S.
        A validated proton beam therapy patch-field protocol for effective treatment of large hepatocellular carcinoma.
        J Radiat Res. 2018; 59: 632-638
        • Colbert L.E.
        • Cloyd J.M.
        • Koay E.J.
        Proton beam radiation as salvage therapy for bilateral colorectal liver metastases not amenable to second-stage hepatectomy.
        Surgery. 2017; 161: 1543-1548
        • Lee C.H.
        • Hung S.P.
        • Hong J.H.
        How small is TOO small? New liver constraint is needed- Proton therapy of hepatocellular carcinoma patients with small normal liver.
        PLoS ONE. 2018; 13e0203854
        • Hsieh C.E.
        • Venkatesulu B.P.
        • Lee C.H.
        Predictors of radiation-induced liver disease in eastern and western patients with hepatocellular carcinoma undergoing proton beam therapy.
        Int J Radiat Oncol Biol Phys. 2019; 105: 73-86
        • Bert C.
        • Durante M.
        Motion in radiotherapy: particle therapy.
        Phys Med Biol. 2011; 56: R113-R144
        • Fukuda K.
        • Okumura T.
        • Abei M.
        Long-term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma.
        Cancer Sci. Mar 2017; 108: 497-503
        • Pfeiler T.
        • Ahmad Khalil D.
        • Ayadi M.
        Motion effects in proton treatments of hepatocellular carcinoma-4D robustly optimised pencil beam scanning plans versus double scattering plans.
        Phys Med Biol. 2018; 63235006
        • McGowan S.E.
        • Burnet N.G.
        • Lomax A.J.
        Treatment planning optimisation in proton therapy.
        Br J Radiol. 2013; 8620120288
        • Gérard J.P.
        • Conroy T.
        • Bonnetain F.
        Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203.
        J Clin Oncol. 2006; 24: 4620-4625
        • Gray B.
        • Van Hazel G.
        • Hope M.
        Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.
        Ann Oncol. 2001; 12: 1711-1720
        • Van Hazel G.
        • Blackwell A.
        • Anderson J.
        Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer.
        J Surg Oncol. 2004; 88: 78-85
        • Hendlisz A.
        • Van den Eynde M.
        • Peeters M.
        Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy.
        J Clin Oncol. 2010; 28: 3687-3694
        • van Hazel G.A.
        • Pavlakis N.
        • Goldstein D.
        Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy.
        J Clin Oncol. 2009; 27: 4089-4095
        • Zou J.
        • Zhu W.
        • Meng H.
        Efficacy and safety of selective internal radiotherapy versus sorafenib for intermediate-locally advanced hepatocellular carcinoma: a systematic review and meta-analysis.
        Expert Rev Gastroenterol Hepatol. 2019; 13: 271-279
        • Kennedy A.
        • Brown D.B.
        • Feilchenfeldt J.
        Safety of selective internal radiation therapy (SIRT) with yttrium-90 microspheres combined with systemic anticancer agents: expert consensus.
        J Gastrointest Oncol. 2017; 8: 1079-1099
        • Formenti S.C.
        • Demaria S.
        Combining radiotherapy and cancer immunotherapy: a paradigm shift.
        J Natl Cancer Inst. 2013; 105: 256-265